Neuropeptidergic Control of Feeding: Focus on the Galanin Family of Peptides

Obesity/overweight are important health problems due to metabolic complications. Dysregulation of peptides exerting orexigenic/anorexigenic effects must be investigated in-depth to understand the mechanisms involved in feeding behaviour. One of the most important and studied orexigenic peptides is galanin (GAL). The aim of this review is to update the mechanisms of action and physiological roles played by the GAL family of peptides (GAL, GAL-like peptide, GAL message-associated peptide, alarin) in the control of food intake and to review the involvement of these peptides in metabolic diseases and food intake disorders in experimental animal models and humans. The interaction between GAL and NPY in feeding and energy metabolism, the relationships between GAL and other substances involved in food intake mechanisms, the potential pharmacological strategies to treat food intake disorders and obesity and the possible clinical applications will be mentioned and discussed. Some research lines are suggested to be developed in the future, such as studies focused on GAL receptor/neuropeptide Y Y1 receptor interactions in hypothalamic and extra-hypothalamic nuclei and sexual differences regarding the expression of GAL in feeding behaviour. It is also important to study the possible GAL resistance in obese individuals to better understand the molecular mechanisms by which GAL regulates insulin/glucose metabolism. GAL does not exert a pivotal role in weight regulation and food intake, but this role is crucial in fat intake and also exerts an important action by regulating the activity of other key compounds under conditions of stress/altered diet

New developments in the management of schizophrenia and bipolar disorder: potential use of cariprazine

Felix-Martin Werner,1,2 Rafael Coveñas2 1Euro Akademie Pößneck, Higher Vocational School for Elderly Care and Occupational Therapy, Pößneck, Germany; 2Institute of Neurosciences of Castilla y León (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems (Lab. 14), University of Salamanca, Salamanca, Spain Abstract: Cariprazine is a recently developed antipsychotic drug with a partial agonism for the D2 and D3 receptors. It shows a tenfold greater affinity for the D3 receptor. In clinical trials, its therapeutic effect has been tested in patients with an acute exacerbation of schizophrenia and in patients with acute mania in bipolar disorder. Like risperidone, cariprazine improves positive and negative schizophrenic symptoms, and ameliorates cognitive functions. Cariprazine induces extrapyramidal symptoms less often than risperidone and can cause acute akathisia. It is a prolactin-sparing antipsychotic drug and has a favorable metabolic profile. In acute mania in bipolar disorder, it treats manic symptoms significantly better than placebo. As a consequence of its improved adverse effects, cariprazine improves patients’ quality of life to a greater extent than other second-generation antipsychotic drugs. Cariprazine is a promising antipsychotic drug in the treatment of schizophrenia, acute mania in bipolar disorder, and in schizophrenia with mania. In these patients, its long-term therapeutic effect and its action in comparison with other second-generation antipsychotic drugs, above all aripiprazole, remain to be tested in clinical trials. Keywords: cariprazine, second-generation antipsychotic drug, schizophrenia, acute mania, D2 receptor, D3 receptor, partial agonism, akathisia, metabolic parameters, cognitive function&nbsp

Modifications in the distribution of met-enkephalin in the cat spinal cord after administration of clonidine. An immunocytochemical study

We have studied the modifications in the distribution of methionine-enkephalin in the cat spinal cord after intravenous or intrathecal administration of clonidine by using an immunocytochemical technique. In animals not treated with the substance, a very high density of immunoreactive fibers was found in layers I and 11; a high density in the dorso-lateral funiculus and in the reticular formation; a moderate density in layers 111, IV and V; and a low density in layer VI. However, after intravenous or intrathecal administration of clonidine a decrease in fibers containing met-enkephalin was observed in layers I and I1 (high or moderate density), the dorso-lateral funiculus, and the reticular formation (moderate or low density), and in layers IV and V (low or very low density). In all cases, the decrease in the immunoreactivity was more marked when clonidine was administered intrathecally. Our results suggest that clonidine induces the release of metenkephalin in the spinal cord. They further suggest that the opioid peptide released could be involved in the control of nociceptive transmission by inhibiting the release of neurotransmitters (e.g., substance P). In summary, our study shows that clonidine could be involved in antinociceptive mechanisms in the cat spinal cord

The involvement of the substance P/neurokinin 1 receptor system in viral infection: focus on the gp120 fusion protein and homologous dipeptide domains.

The human immunodeficiency virus (HIV) envelope, via a key extracellular amino acid sequence, may simulate the functionality of native undecapeptide substance P (SP) acting through the host's neurokinin 1 (SP preferring) receptor (NK-1R). Human monocytes and macrophages express both NK-1Rs and SP. In HIV/AIDS the NK-1R may function as a chemokine-like G-protein coupled co-receptor that: 1) fuses to the outer envelope of HIV; 2) enables intracellular entry of the envelope-capsid-NK-1R complex; 3) co-opts immune defence via its physiological interaction with the SP-like envelope; 4) may contribute to resistance of CD4/chemokine entry inhibitor type drugs; 5) relaxes the blood-brain barrier to support entry of the HIV into the central nervous system, and 6) mediates most of the common clinical sequelae of HIV/AIDS (encephalopathy and AIDS dementia complex). The data support the idea that NK-1R antagonists could be useful to treat HIV/AIDS. Keywords: human immunodeficiency virus; NK-1 receptor; NK-1 receptor antagonist; aprepitant; fusion protein; virus

The involvement of the substance P/neurokinin 1 receptor system in viral infection: focus on the gp120 fusion protein and homologous dipeptide domains

The human immunodeficiency virus (HIV) envelope, via a key extracellular amino acid sequence, may simulate the functionality of native undecapeptide substance P (SP) acting through the host's neurokinin 1 (SP preferring) receptor (NK-1R). Human monocytes and macrophages express both NK-1Rs and SP. In HIV/AIDS the NK-1R may function as a chemokine-like G-protein coupled co-receptor that: 1) fuses to the outer envelope of HIV; 2) enables intracellular entry of the envelope-capsid-NK-1R complex; 3) co-opts immune defence via its physiological interaction with the SP-like envelope; 4) may contribute to resistance of CD4/chemokine entry inhibitor type drugs; 5) relaxes the blood-brain barrier to support entry of the HIV into the central nervous system, and 6) mediates most of the common clinical sequelae of HIV/AIDS (encephalopathy and AIDS dementia complex). The data support the idea that NK-1R antagonists could be useful to treat HIV/AIDS. Keywords: human immunodeficiency virus; NK-1 receptor; NK-1 receptor antagonist; aprepitant; fusion protein; virus

Role Of Neuropeptides In Migraine: Where Do They Stand In The Latest Expert Recommendations In Migraine Treatment?

Many factors have been implicated in the pathogenesis of migraine headache, including activation of the trigeminovascular system, dysfunction of: cerebral blood vessels, circulating vasoactive substances, mitochondrial energy metabolism, brain oxygenation and metabolism, platelet disorder, alterations in serotonin levels, low levels of brain tissue magnesium, altered transport of ions across the cell membrane, and inheritance and dysfunction of the brainstem periaqueductal gray matter. The headache phase of migraine is associated with cerebral vasodilation and inflammation, presumably mediated by the release of vasoactive substances and neuropeptides including CGRP (calcitonin gene-related peptide). Increased serum CCRP levels have been detected during migraine and cluster headache. One strategy to treat migraine is to inhibit the release of neuropeptides or to block their receptors. This article briefly reviews some experimental and clinical investigations focused on neuropeptide involvement in migraine. © 2007 Wiley-Liss, Inc